RESEARCH & RELATED - OTHER PROJECT INFORMATION - PROJECT SUMMARY/ABSTRACT This Core B facility will serve as a technical and scientific support unit for the three projects (1, 2, 3) of this Program Project. Its major goals involve: (1) the re-synthesis and scale-up of compounds in sufficient quantifies to address the in vitro and in vivo needs of the research laboratories involved in the four projects; all compounds will be evaluated in silico for their druggability properties as well (2) the testing of all new ligands for their affinities for the CB1 and CB2 cannabinoid receptors; (3) the testing of ligands for their abilities to bind irreversibly to CB1 and CB2; (4) the testing of a class of ligands for their abilities to act as substrates or inhibitors for the endocannabinoid deactivating enzymes, FAAH and MGL; (5) determining the functional properties of successful ligands initially in the cAMP assay; (6) determining the biochemical stabilities of ligands using liver microsomal preparations; (7) evaluation of a select group of novel ligands in mice for bioavailability and their ability to cross the blood brain barrier; and (8) evaluation of CB1 antagonists in vivo (mice) for their ability to antagonize the effects of an agonist. Compounds produced under the auspices of Core B will also be made available to other laboratories identified in this program project whose collaboration is at no cost to the grant.